Recent data support the possibility of inducing a remission in a large number of RA patients receiving combination therapy; this data supports the need and the design of this "Rheumatoid Arthritis Induction Trial with methotrexate and anti-TNF therapy (RAITMAT) study. Our hypothesis is that patients with early rheumatoid arthritis (RA) when treated with a combination of methotrexate, anti-tumor necrosis factor (anti-TNF) agent and oral corticosteroids will be able to induce a remission in 50% of subjects at 12 months, and that 50% there subjects will remain in remission at least 12 months after discontinuing the anti-TNF agent in a blinded manner. This important study will establish the most cost effective ways to manage early RA patients, while avoiding intermediate-term joint damage, disability and unemployment. The anti-TNF free holidays may also minimize serious adverse events, such as infections. In addition, we will propose state of the art mechanistic studies that will provide the framework for studying the disease and its variability among subjects, as well as potential biomarkers that might be useful to predict response (or lack of response) to this induction therapy. A steering committee of clinical trialists, biostatisticians, and basic researchers has been formed to design the RAITMAT trial. A clinical trials planning grant is needed for the following specific aims: 1.) Conduct meetings and teleconferences of the steering committee to write the grants needed for funding of the RAITMAT trial; 2.) Develop study materials such as manual of operations & procedures, quality control procedures, informed consent prototype, and data collection instruments; 3.) Secure study medications from pharmaceutical/biotech companies; and 4.) Finalize mechanistic studies to be performed. This proposal brings together an experienced group of investigators involved with RA research. We will prospectively analyze the molecular signatures of responses to treatment with combinations of RA therapies that will induce remission. The results of these studies will provide novel information on best treatment approaches in patients with early aggressive RA. An important objective of the proposed trial will be to identify proteomic and/or genomic biomarkers to guide patient selection and therapy. Technologies to be evaluated include autoantibody, cytokine, mRNA, and other biomarker profiling technologies. This project seeks to gather intellectual expertise to develop mechanism and protocol by which to evaluate mechanistic studies and potential biomarkers for evidence of the short term benefits of powerful treatment regimens used in the course of early aggressive intervention of rheumatoid arthritis. This will lead to the development of the proposed Rheumatoid Arthritis Induction Trial with MTX and Anti-TNF Therapy (RAITMAT). [unreadable] [unreadable] [unreadable] [unreadable]